Translation of the abstract (English)

During anesthesia with isoflurane or sevoflurane there is a “luxury perfusion in the brain”, due to these volatile anesthetics causing cerebral vasodilatation. Since the increase in cerebral blood-flow in mice during anesthesia with isoflurane can be reduced by a nonspecific inhibitor of NO-synthase, this effect is suspected to be mediated by NO. In rats anesthesia with isoflurane or sevoflurane ...

Translation of the abstract (English)

During anesthesia with isoflurane or sevoflurane there is a “luxury perfusion in the brain”, due to these volatile anesthetics causing cerebral vasodilatation. Since the increase in cerebral blood-flow in mice during anesthesia with isoflurane can be reduced by a nonspecific inhibitor of NO-synthase, this effect is suspected to be mediated by NO. In rats anesthesia with isoflurane or sevoflurane leads to an increase of NO in the cerebral cortex, that can be reduced as well by a nonspecific inhibitor of NO-synthase. In addition the observation was made that in rats that served as controls the cerebral blood volume increased gradually during repeatedly given anesthesia with isoflurane. The goal of this study was to find out in cell-culture of human cerebral endothelial cells if this gradual increase of cerebral blood volume during repeatedly given anesthesia with volatile anesthetics was caused by changes in the NO-pathway.
Therefore hCMEC/D3-cells, an immortalized cell-culture of human cerebral endothelial cells with specific characteristics of the blood-brain-barrier, were exposed once, twice or three times to 1 or 2 MAC isoflurane or sevoflurane for one hour with an interval of 12 hours. After that the production of NO was measured in the cell media by colorimetric griess-assay and GC-MS-measurement as well as the expression of iNOS and eNOS were analyzed by western-blotting.
There was no effect detectable. The reason for this remains obscure. On one hand it could be possible that the increase of NO that was seen in vivo was due to glia-cells and not to endothelial cells. On the other hand it could be possible as well that the specific characteristics of the blood-brain-barrier of the hCMEC/D3 had undergone dedifferentiation in cell-culture.
Furthermore it was shown via experiments with hypoxia that significant differences in the expression of eNOS were measurable in our experiments - if existing. The behavior of the hCMEC/D3 with a significant decrease of eNOS-expression (1,93 +/- 0,69 compared to 1,02 +/- 0,38 during hypoxia (p < 0,05)) and no measurable increase in iNOS-expression during 24h-hypoxia, couldn’t be correlated with the behavior of other cerebral endothelial cells or endothelial cells of other regions of the body as described in literature. These results possibly indicate that the hCMEC/D3 had undergone dedifferentiation.
Further experiments with non-immortalized cerebral endothelial cells might explain the correlation between exposure to volatile anesthetics and expression of eNOS or iNOS.